NM_024675.4(PALB2):c.2834+5G>A AND Familial cancer of breast

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000635658.9

Allele description

NM_024675.4(PALB2):c.2834+5G>A

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.2834+5G>A

HGVS:

NC_000016.10:g.23624004C>T
NG_007406.1:g.22354G>A
NM_024675.4:c.2834+5G>AMANE SELECT
LRG_308t1:c.2834+5G>A
LRG_308:g.22354G>A
NC_000016.9:g.23635325C>T
NM_024675.3:c.2834+5G>A

Links:

dbSNP: rs570455216

NCBI 1000 Genomes Browser:

rs570455216

Molecular consequence:

NM_024675.4:c.2834+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Homo sapiens TNF receptor superfamily member 25 (TNFRSF25), transcript variant 1...
Homo sapiens TNF receptor superfamily member 25 (TNFRSF25), transcript variant 1, mRNA
gi|1890258826|ref|NM_148965.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000757079	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34846068, 17576681, 9536098, 28492532
SCV005053885	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 18, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000757079

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 4, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV005053885

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 18, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing predictions, minigene analyses, and ACMG-AMP clinical classification of 42 germline PALB2 splice-site variants.

Valenzuela-Palomo A, Bueno-Martínez E, Sanoguera-Miralles L, Lorca V, Fraile-Bethencourt E, Esteban-Sánchez A, Gómez-Barrero S, Carvalho S, Allen J, García-Álvarez A, Pérez-Segura P, Dorling L, Easton DF, Devilee P, Vreeswijk MP, de la Hoya M, Velasco EA.

J Pathol. 2022 Mar;256(3):321-334. doi: 10.1002/path.5839. Epub 2021 Dec 28. Erratum in: J Pathol. 2023 Nov;261(3):372-373. doi: 10.1002/path.6215.

PubMed [citation]

PMID:: 34846068
PMCID:: PMC9306493

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000757079.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change falls in intron 8 of the PALB2 gene. It does not directly change the encoded amino acid sequence of the PALB2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs570455216, gnomAD 0.03%). This variant has been observed in individual(s) with breast cancer (PMID: 34846068). ClinVar contains an entry for this variant (Variation ID: 530057). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV005053885.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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